1. Field of the Invention
The present invention relates generally to the fields of cardiovascular medicine and the chemistry of salicylates. More specifically, the present invention relates to novel analogues of acetylsalicylic acid and novel uses thereof.
2. Description of the Related Art
There is little literature other than the work of Reinhart and Chien (1986) concerning the effect of salicylates on rheological properties of red blood cells. Reinhart and Chien incubated red blood cells in vitro with very high concentrations (from 7.5 mM to 120 mM) of sodium salicylate, and found that there was a considerable decrease in the mean cell transit times of red blood cells while flowing through narrow capillaries. This observation is qualitatively in agreement with a more recent clinical study involving intake of aspirin by ten healthy human subjects (vide infra). However, the important difference between the two results is that the clinical study dealt with a salicylate concentration of the order of only 0.7 mM in whole blood, in addition to not accounting for adsorption of aspirin by tissues other than red blood cells. Furthermore, whereas no morphologic changes were observed in the red cells from their diskocyte form in the clinical study, Reinhart and Chien observed a definite echinocytic transformation. In fact, the latter researchers cite the change in morphology, i.e., the development of excess surface area, as the cause for the ease of flow of the red cells through the capillaries. This phenomenon of large shape changes at the high salicylate concentrations is but an extreme limit of the process that begins at the lower concentrations, namely the alteration of the membrane constitution and a lowering of the membrane viscoelastic properties. A speculative mechanism is that aspirin might acylate the membrane and this would not be unreasonable, based on the documented chemical property of aspirin to acylate proteins, including hemoglobins (Zaugg, et al., 1980).
Aspirin, a most common household drug, has long been known to improve blood circulation but the mechanism by which it does so has largely been a mystery. It is well known that the narrowing of arteries, resulting from the build-up of fatty acids, cholesterol, and scar tissues (atheroscerosis) inside the walls of the arteries, is one of the major factors responsible for inadequate blood supply or circulation (ischemia) that leads to major pathologies of the industrialized western world, such as heart attack (myocardial infarction), cerebrovascular disease (stroke or apoplexy), cramping pain of leg and calf muscles (intermittent claudication), recurrent chest pain (angina pectoris) and dry gangrene.
The prior art is deficient in the lack of effective means of decreasing the mean cell transit time of erythrocytes and thereby treating various cardiovascular diseases. The present invention fulfills this longstanding need and desire in the art.